The tyrosine kinase system angiopoietin（Ang）/Tie interacts with vascular endothelial growth factor pathway and regulates vessel quiescence in adults as well as later steps of the angiogenic cascade related to vessel...The tyrosine kinase system angiopoietin（Ang）/Tie interacts with vascular endothelial growth factor pathway and regulates vessel quiescence in adults as well as later steps of the angiogenic cascade related to vessel maturation. Since all Angs are able to bind to Tie-2 but none binds to Tie-1,the function of Tie-2 and its ligands have captured attention. However,emerging evidence indicates unique roles of the orphan receptor Tie-1 in angiogenesis under physiological and pathological conditions. It is required for maintaining vascular endothelial cell integrity and survival during murine embryo development and in adult and may be involved in modulating differentiation of hematopoietic cells in adult. Tie-1 exhibits poor tyrosine kinase activity and signals via forming heterodimers with Tie-2,inhibiting Tie-2 signaling mediated by Angs. This inhibition can be relieved by Tie-1 ectodomain cleavage mediated by tumor- and inflammatory-related factors,which causes destabilization of vessels and initiates vessel remodeling. Up-regulated Tie-1 expression has been found not only in some leukemia cells and tumor related endothelial cells but also in cytoplasm of carcinoma cells of a variety of human solid tumors,which is associated with tumor progression. In addition,it has pro-inflammatory functions in endothelial cells and is involved in some inflammatory diseases associated with angiogenesis. Recent research indicated that Tie-1 gene ablation exhibited significant effects on tumor blood- and lymph-angiogenesis and improved anti-Ang therapy,suggesting Tie-1 may be a potential target for tumor anti-angiogenesis treatment.展开更多
目的探讨基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2，TIMP-2）基因启动子区单核苷酸多态性与子宫内膜异位症和子宫腺肌病发病风险的关系。方法采用PCR...目的探讨基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2，TIMP-2）基因启动子区单核苷酸多态性与子宫内膜异位症和子宫腺肌病发病风险的关系。方法采用PCR-限制性片段长度多态方法检测298例子宫内膜异位症患者（内异症组）、180例子宫腺肌病患者（腺肌病组）和324名对照妇女（对照组）MMP-2和TIMP-2基因型频率的分布。结果MMP-2—1306C／T多态的基因型和等位基因频率分布在子宫内膜异位症组与对照组间差异无统计学意义（P〉0．05）；但在腺肌病组和对照组间MMP-2—1306C／T多态的基因型和等位基因频率分布均有明显的差异（P〈0．05）；与CT＋TT基因型相比，CC基因型明显增加腺肌病的发病风险，OR值为1．83（95％CI：1．13～2．96）。MMP-2—735C／T多态的基因型和等位基因频率分布在3组间均未发现明显差异（P〉0．05）；统计学分析显示MMP-2基因的2个多态性位点间存在着连锁不平衡（D＇=0．74），但4种单倍型频率在3组之间分布差异无统计学意义（P〉0．05）。TIMP-2—418G／C多态的等位基因频率分布在3组间差异无统计学意义（P〉0．05），但CC基因型频率在子宫内膜异位症组患者中为0．7％，与对照组（3．7％）比较，差异有统计学意义（P〈0．05）。结论MMP-2—1306C／T多态C等位基因的存在可明显增加腺肌病的发病风险，但与子宫内膜异位症的发病风险无关；MMP-2—735C／T和TIMP-2—418G／C多态与子宫内膜异位症和腺肌病的发病风险无明显关联。展开更多
基金supported by grants from the Fundamental Research Funds for the Central Universities(HUST:2015ZHYX015)the National Natural Science Foundation of China(No.81272860)
文摘The tyrosine kinase system angiopoietin（Ang）/Tie interacts with vascular endothelial growth factor pathway and regulates vessel quiescence in adults as well as later steps of the angiogenic cascade related to vessel maturation. Since all Angs are able to bind to Tie-2 but none binds to Tie-1,the function of Tie-2 and its ligands have captured attention. However,emerging evidence indicates unique roles of the orphan receptor Tie-1 in angiogenesis under physiological and pathological conditions. It is required for maintaining vascular endothelial cell integrity and survival during murine embryo development and in adult and may be involved in modulating differentiation of hematopoietic cells in adult. Tie-1 exhibits poor tyrosine kinase activity and signals via forming heterodimers with Tie-2,inhibiting Tie-2 signaling mediated by Angs. This inhibition can be relieved by Tie-1 ectodomain cleavage mediated by tumor- and inflammatory-related factors,which causes destabilization of vessels and initiates vessel remodeling. Up-regulated Tie-1 expression has been found not only in some leukemia cells and tumor related endothelial cells but also in cytoplasm of carcinoma cells of a variety of human solid tumors,which is associated with tumor progression. In addition,it has pro-inflammatory functions in endothelial cells and is involved in some inflammatory diseases associated with angiogenesis. Recent research indicated that Tie-1 gene ablation exhibited significant effects on tumor blood- and lymph-angiogenesis and improved anti-Ang therapy,suggesting Tie-1 may be a potential target for tumor anti-angiogenesis treatment.
文摘目的探讨基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2，TIMP-2）基因启动子区单核苷酸多态性与子宫内膜异位症和子宫腺肌病发病风险的关系。方法采用PCR-限制性片段长度多态方法检测298例子宫内膜异位症患者（内异症组）、180例子宫腺肌病患者（腺肌病组）和324名对照妇女（对照组）MMP-2和TIMP-2基因型频率的分布。结果MMP-2—1306C／T多态的基因型和等位基因频率分布在子宫内膜异位症组与对照组间差异无统计学意义（P〉0．05）；但在腺肌病组和对照组间MMP-2—1306C／T多态的基因型和等位基因频率分布均有明显的差异（P〈0．05）；与CT＋TT基因型相比，CC基因型明显增加腺肌病的发病风险，OR值为1．83（95％CI：1．13～2．96）。MMP-2—735C／T多态的基因型和等位基因频率分布在3组间均未发现明显差异（P〉0．05）；统计学分析显示MMP-2基因的2个多态性位点间存在着连锁不平衡（D＇=0．74），但4种单倍型频率在3组之间分布差异无统计学意义（P〉0．05）。TIMP-2—418G／C多态的等位基因频率分布在3组间差异无统计学意义（P〉0．05），但CC基因型频率在子宫内膜异位症组患者中为0．7％，与对照组（3．7％）比较，差异有统计学意义（P〈0．05）。结论MMP-2—1306C／T多态C等位基因的存在可明显增加腺肌病的发病风险，但与子宫内膜异位症的发病风险无关；MMP-2—735C／T和TIMP-2—418G／C多态与子宫内膜异位症和腺肌病的发病风险无明显关联。
